Dr. Giulio Porcedda (Pediatric and Transitional Cardiology, A.O.U. Meyer, Florence) in his presentation titled “Cardiological Aspects Highlighted in Patients with COL4A1-A2” described the cardiological aspects in patients with COL4A1 and COL4A2. He initially focused on the multidisciplinary nature of the pathology and how recently there has been an increasing focus on these diseases, resulting in a growing number of diagnosed patients due to improving diagnostic methods. In 2015, there were only 174 patients identified in the literature. By 2023, there were 269 pathogenic variants and 64 VUS (variants of uncertain significance), 25 of which were type 2. He then defined the role of the heart in these pathologies. An article suggests that the extracellular matrix, rich in type IV collagen, also affects the heart, involving multiple aspects: angiopathy, atherosclerosis, hypertension, mitral valve prolapse, aortic dilation, aneurysms, tachycardia, and fibrillation. Some of these conditions can be associated, while others are dependent.

Dr. Porcedda’s group then studied a cohort of 43 individuals from 23 families, all identified with pathogenic or near-pathogenic variants. All were given a questionnaire and underwent extensive investigation. To study this cohort, they conducted ophthalmologic and cardiologic screenings on both symptomatic and asymptomatic patients, aiming to develop a prevention and management protocol involving as many organs as possible. They found data consistent with the literature, particularly a 6% cardiovascular involvement, with 39 out of 647 published patients. There were 11 patients with heart defects, many of which are common in the general population, such as the patent foramen ovale, present in 30% of people. Other true septal defects seemed predominant and characteristic of the pathology, such as cor triatriatum, which separates the atrium with a membrane, and hypertrophic cardiomyopathies.

Valves were involved due to their collagen richness. The arterial duct was a common association in young children. Two adults with mitral valve prolapse showed valve involvement. Atrial fibrillation was present in 1% of individuals, with 8 out of 647 patients having supraventricular tachycardias. They also found overlaps with Marfan syndrome. In this cohort, they identified 43 individuals, six of whom (five with COL4A1 and one with COL4A2) had cardiovascular manifestations. Five of them had arterial hypertension and atrial fibrillation, while one had acute coronary syndrome. Only one patient had an atrial septal defect requiring surgery. Arrhythmias were found only in adult patients.

A complete cardiological evaluation was then performed on all patients, with one adult patient having atrial fibrillation. Other patients had normal results, suggesting that arrhythmias might just be associations. An echocardiogram revealed aortic sclerosis in one adult patient, common with ageing. Mitral valves and aortic dilations were also present.

Dr. Porcedda and his collaborators’ study showed a higher incidence of heart diseases compared to the general population, though not all patients were affected. Visceral arterial aneurysms, coronary dissections, and other cardiovascular diseases were more common in adulthood.

Dr. Porcedda concluded his presentation by proposing a complete cardiological evaluation at diagnosis and, if negative, a repeat every 3-4 years for all patients with COL4A1 and COL4A2 mutations. In case of symptoms, ECG and stress tests are recommended, along with blood pressure measurement and cardiac MRI for arrhythmias.